晚期糖基化终产物对缺氧条件下内皮细胞血管生成能力的影响

目的明确晚期糖基化终产物(AGE)对缺氧条件下内皮细胞血管生成能力的影响,并探讨其可能机制。方法将酶消化法分离、培养的大鼠心肌微血管内皮细胞随机分为5组,对照组、AGE组、缺氧组、AGE+缺氧组、抑制剂组。MTT法测定细胞增殖能力;Transwell法检测细胞迁移;管样结构形成实验观察血管生成能力;Westernblot检测细胞外信号调节激酶(ERK)5磷酸化水平;ELISA检测血管内皮细胞生长因子(VEGF)分泌。结果与对照组比较,缺氧组内皮细胞的增殖、迁移、管样结构形成能力和VEGF分泌水平显著提高。与AGE+缺氧组比较,抑制剂组内皮细胞的增殖、迁移、管样结构形成能力增强,ERK5磷酸化水平明显降低,VEGF分泌水平增加。结论 AGE可抑制缺氧条件下内皮细胞的血管生成能力,其机制可能与ERK5的磷酸化抑制VEGF的表达有关。

Effect of advanced glycation end products on angiogenesis of endothelial cells exposed to hypoxia

Objective To study the effect of advanced glycation end(AGE) products on angiogenesis of endothelial cells(EC) exposed to hypoxia and its potential mechanism.Methods Cultured rat EC isolated by enzyme digestion were divided into control group,AGE products group,hypoxia group,AGE products+hypoxia group,and inhibition group.Proliferation and migration of EC were detected by MTT and transwell assay,respectively.Angiogenesis of EC was observed in tube formation experiment.Extracellular signal-regulated ERK5 phosphorylation was assayed by Western blot.Intravascular VEGF secretion was measured by ELISA.Results The proliferation and migration of EC,tube formation and VEGF secretion in EC were significantly higher whereas the ERK5 phosphorylation was significantly lower in hypoxia group and inhibition group than in control group and AGE products+hypoxia group.Conclusion AGE products can inhibit angiogenesis of EC exposed to hypoxia,which may be related to the inhibition of VEGF expression due to ERK5 phosphorylation.